發(fā)布時(shí)間：2018-04-28 18:15

  本文選題：布舍瑞林 + 固液相�。� 參考：《蘇州大學(xué)》2014年碩士論文

【摘要】：在歐美發(fā)達(dá)國(guó)家，前列腺癌的發(fā)病率高居男性惡性腫瘤第2位，在亞洲國(guó)家則相對(duì)較低，但呈上升趨勢(shì)。研究資料顯示，全球每年死于前列腺癌的患者人數(shù)達(dá)到25.8萬(wàn)。隨著國(guó)民經(jīng)濟(jì)的發(fā)展和生活方式的改變，我國(guó)男性前列腺癌發(fā)病率已從1993年的1.71/10萬(wàn)上升至2010年的10/10萬(wàn)，形勢(shì)不容樂(lè)觀。與此同時(shí)，乳腺癌、子宮內(nèi)膜異位癥及子宮肌瘤等婦科疾病也影響著全球女性的健康。世衛(wèi)組織官方網(wǎng)站資料顯示，全球每年新增乳腺癌患者約138萬(wàn)，年死亡人數(shù)為45.8萬(wàn)。我國(guó)婦女的乳腺癌發(fā)病率約為21.6/10萬(wàn)，，子宮內(nèi)膜異位癥患者占到育齡婦女的10~15%，有20~30%的成年女性患有不同程度的子宮肌瘤。這些性激素依賴性疾病不僅給患者身體帶來(lái)了嚴(yán)重病痛，也極大影響了他們的生活質(zhì)量。 GnRH(促性腺激素釋放激素)類似物自問(wèn)世以來(lái)，由于具備活性高，用量少，不良反應(yīng)小及療效穩(wěn)定等優(yōu)勢(shì)，在性激素依賴性疾病的治療中發(fā)揮著重要作用。根據(jù)作用機(jī)制不同，GnRH類似物均為多肽，分為兩類，一類是GnRH激動(dòng)劑，如曲普瑞林，布舍瑞林，戈舍瑞林，亮丙瑞林等；另一類是GnRH拮抗劑，如西曲瑞克，加尼瑞克，阿巴瑞克等。這些專利多肽藥帶來(lái)良好療效的同時(shí)，其昂貴的價(jià)格也給發(fā)展中國(guó)家的患者帶來(lái)了沉重的經(jīng)濟(jì)負(fù)擔(dān)。為此，開(kāi)發(fā)價(jià)格低廉并具備同等質(zhì)量和療效的仿制藥，具有重要的現(xiàn)實(shí)意義。布舍瑞林由法國(guó)賽諾菲-安萬(wàn)特公司研制生產(chǎn)，于1984年首次在德國(guó)上市，目前主要在歐洲，亞洲，部分拉丁美洲和非洲國(guó)家銷售，在美國(guó)處于臨床三期階段�；谄淞己玫寞熜Ш褪袌�(chǎng)銷售，并且專利保護(hù)即將到期，本論文在查閱相關(guān)文獻(xiàn)和專利的基礎(chǔ)上，采用固液相結(jié)合的技術(shù)，設(shè)計(jì)和優(yōu)化了一種新的布舍瑞林合成路線。該路線操作簡(jiǎn)便，生產(chǎn)周期短，產(chǎn)品純度和收率均較高，成本較低，易于放大生產(chǎn),能在一定程度上帶動(dòng)布舍瑞林原料藥的市場(chǎng)銷售價(jià)格的下降，從而對(duì)其成品藥價(jià)格的進(jìn)一步降低起到積極促進(jìn)作用，有利于減輕患者的經(jīng)濟(jì)負(fù)擔(dān)。
[Abstract]:In the developed countries of Europe and America, the incidence of prostate cancer is the second highest in men with malignant tumor, but it is relatively low in Asian countries, but it is on the rise. According to the study, the number of people dying of prostate cancer every year in the world reached 258000. With the development of national economy and the change of life style, the incidence of prostate cancer in men in China has risen from 17.1 / 100 thousand in 1993 to 10 / 100 thousand in 2010. The situation is not optimistic. At the same time, gynecological diseases such as breast cancer, endometriosis and hysteromyoma affect women's health around the world. According to WHO's official website, there are about 1.38 million new cases of breast cancer worldwide each year, with 458000 deaths per year. The incidence of breast cancer in women in China is about 21.6 / 100 thousand. Endometriosis patients account for 10, 15 women of childbearing age, and 20% of adult women have different degrees of uterine leiomyoma. These sex hormone-dependent diseases not only bring serious pain to patients, but also greatly affect their quality of life. GnRH (gonadotropin releasing hormone) analogue has played an important role in the treatment of gonadotropin-dependent diseases because of its advantages of high activity, low dosage, small adverse reaction and stable curative effect. The GnRH analogues are polypeptides according to their mechanism of action, one is GnRH agonists, such as troplin, Buserelin, Goserelin, Leuprilline, and the other is GnRH antagonists, such as citrork, ganirk, and so on. Abalic, etc. While these patented polypeptide drugs have good efficacy, their high prices also impose a heavy economic burden on patients in developing countries. Therefore, it is of great practical significance to develop low-cost generic drugs with the same quality and efficacy. Buserelin, which was developed and manufactured by France's Sanofi-Aventis, was first listed in Germany in 1984. It is currently mainly sold in Europe, Asia, some Latin American and African countries, and is in the third phase of the clinical phase in the United States. Based on its good effect and marketing, and the expiration of patent protection, a new synthesis route of Buserelin is designed and optimized based on the review of relevant literatures and patents. This route is easy to operate, short production cycle, high product purity and yield, low cost, easy to enlarge production, and can lead to the decrease of market sales price of Buserelin API to a certain extent. Thus, the further reduction of the price of its finished medicine plays an active role in reducing the economic burden of patients.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 姜和;吳洋;陸榮健;;多肽“困難序列”的合成研究進(jìn)展[J];重慶理工大學(xué)學(xué)報(bào)(自然科學(xué));2011年05期

2 史精華;冷金花;;促性腺激素釋放激素及其受體研究進(jìn)展[J];國(guó)際婦產(chǎn)科學(xué)雜志;2010年01期

3 周宇紅;;蒽環(huán)類藥物的心臟毒性及預(yù)防[J];上海醫(yī)藥;2010年11期

4 陳紅菊;尹伶;;子宮肌瘤病因?qū)W的研究進(jìn)展[J];實(shí)用預(yù)防醫(yī)學(xué);2012年06期

5 潘春紅;;子宮內(nèi)膜異位癥治療現(xiàn)狀和展望[J];醫(yī)學(xué)綜述;2009年21期

6 陳瑞寶;劉繼紅;;藥物治療前列腺癌進(jìn)展[J];醫(yī)藥導(dǎo)報(bào);2011年04期

7 郭紅宇,高云荷;GnRH類似物的研究進(jìn)展[J];中國(guó)實(shí)用婦科與產(chǎn)科雜志;2005年11期

8 武國(guó)海;周彩紅;王明偉;;前列腺癌治療藥物的研究新進(jìn)展[J];中國(guó)新藥雜志;2007年17期

9 潘慧;張淵;郭彥琨;張英;;常用細(xì)胞毒性藥物的配伍穩(wěn)定性及使用安全性探討[J];中國(guó)藥師;2011年10期

10 王樝;宋麗君;王舉波;胡珀;李志裕;;用于治療前列腺癌的雄激素受體拮抗劑[J];藥學(xué)進(jìn)展;2012年06期

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